Past approaches to discovering new medicines

A brief account is given of the main approaches to new drug discovery which have been taken during the twentieth century. Four main sources for new drugs are described and each of these is discussed in turn; they are: natural products, existing drugs, screens and physiological transmitters.Se hace una breve historia de las principales aproximaciones al descubrimiento de nuevos fármacos. Se describen cuatro de las principales aproximaciones: productos naturales, uso de prototipos existentes, screening farmacológico y transmisores fisiológicos

Aproximaciones históricas al descubrimiento de nuevos fármacos

Se hace una breve historia de las principales aproximaciones al descubrimiento de nuevos fármacos. Se describen cuatro de las principales aproximaciones: productos naturales, uso de prototipos existentes, screening farmacológico y transmisores fisiológicos.A brief account is given of the main approaches to new drug discovery which have been taken during the twentieth century. Four main sources for new drugs are described and each of these is discussed in turn; they are: natural products, existing drugs, screens and physiological transmitters

Anesthetic-like Interaction of the Sleep-inducing Lipid Oleamide with Voltage-gated Sodium Channels in Mammalian Brain

Results: cOA stereoselectively inhibited specific binding of toxin to VGSC (inhibitor concentration that displaces 50% of specifically bound radioligand, 39.5 M). cOA increased (4؋) the K d of toxin binding without affecting its binding maximum. Rate of dissociation of radioligand was increased without altering association kinetics, suggesting an allosteric effect (indirect competition at site 2 on VGSC). cOA blocked tetrodotoxin-sensitive sodium currents (maximal effect and affinity were significantly greater at depolarized potentials; P < 0.01). Between 3.2 and 64 M, the block was concentration-dependent and saturable, but cOA did not alter the V 50 for activation curves or the measured reversal potential (P > 0.05). Inactivation curves were significantly shifted in the hyperpolarizing direction by cOA (maximum, ؊15.4 ؎ 0.9 mV at 32 M). cOA (10 M) slowed recovery from inactivation, with increasing from 3.7 ؎ 0.4 ms to 6.4 ؎ 0.5 ms (P < 0.001). cOA did not produce frequencydependent facilitation of block (up to 10 Hz). Conclusions: These effects (and the capacity of oleamide to modulate ␥-aminobutyric acid A receptors in earlier studies) are strikingly similar to those of a variety of anesthetics. Oleamide may represent an endogenous ligand for depressant drug sites in mammalian brain

Histamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [75, 163]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [75]. The human and rat H3 receptor genes are subject to significant splice variance [12]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [163]. Some agonists at the human H3 receptor display significant ligand bias [171]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. ZPL-3893787; Phase IIa) [163] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [205, 8]

Histamine receptors in GtoPdb v.2021.3

Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [80, 173]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [80]. The human and rat H3 receptor genes are subject to significant splice variance [12]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [173]. Some agonists at the human H3 receptor display significant ligand bias [182]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. adriforant; Phase IIa) [173] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [216, 8]

Histamine receptors in GtoPdb v.2023.1

Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [80, 174]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [80]. The human and rat H3 receptor genes are subject to significant splice variance [12]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [174]. Some agonists at the human H3 receptor display significant ligand bias [183]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. adriforant; Phase IIa) [174] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [217, 8]

Analogue-based Drug Discovery III

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